The complement system is an enzyme cascade that helps defend against infection. Many complement proteins occur in serum as inactive enzyme precursors (zymogens); others reside on cell surfaces. The complement system bridges innate and acquired immunity by

Classical pathway components are labeled with a C and a number (eg, C1, C3), based on the order in which they were identified. Alternative pathway components are often lettered (eg, factor B, factor D) or named (eg, properdin).

Classical pathway activation is Ab-dependent, occurring when C1 interacts with Ag-IgM or aggregated Ag-IgG complexes, or Ab-independent, occurring when polyanions (eg, heparin, protamine, DNA and RNA from apoptotic cells), gram-negative bacteria, or bound C-reactive protein reacts directly with C1. This pathway is regulated by C1 inhibitor (C1-INH). Hereditary angioedema is due to a genetic deficiency of C1-INH.

The 3 activation pathways converge into a final common pathway when C3 convertase cleaves C3 into C3a and C3b (see Figure: Complement activation pathways.). C3 cleavage may result in formation of the membrane attack complex (MAC), the cytotoxic component of the complement system. MAC causes lysis of foreign cells.

C3b acts as an opsonin by coating microorganisms and thereby enhancing their phagocytosis.

C3d enhances Ab production by B cells.

C5a is a neutrophil chemoattractant; it regulates neutrophil and monocyte activities and may cause augmented adherence of cells, degranulation and release of intracellular enzymes from granulocytes, production of toxic oxygen metabolites, and initiation of other cellular metabolic events.

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